Researchers are steadily cataloging the details of age-related changes in stem cells, which seem to have as much to do with the cellular environment as a whole as the cells themselves: "Aging causes phenotypic changes in skeletal muscle progenitor cells (SMPCs) that lead to the loss of myogenicity and adipogenesis. Secreted protein acidic and rich in cysteine (SPARC), which is secreted from SMPCs, stimulates myogenesis and inhibits adipogenesis. The present study aimed to examine whether changes in SPARC expression, its signaling pathway, or both are involved in age-related phenotypic changes in SMPCs. SPARC expression levels were comparable in SMPCs derived from young and old rats. However, when SPARC expression was reduced by a SPARC-specific siRNA, SMPCs from young rats showed reduced myogenesis and increased adipogenesis. In striking contrast, old rats showed little changes in these functions. ... These results suggest that, although SPARC plays a role in regulating SMPC function, SMPCs become refractory to the action of SPARC with age. Our data may explain an age-related shift from myogenesis to adipogenesis, associated with sarcopenia. ... Because SPARC enhances myogenesis and inhibits adipogenesis, we reasoned that its decreased expression or alterations in its signaling pathway in SMPCs contribute to age-related dysfunction of skeletal muscle, such as fatty infiltration and impaired muscle regeneration. The present study shows that the SPARC signaling pathway, rather than the level of its expression in SMPCs changes with age. It should be noted skeletal muscle cell types other than SMPCs, such as myofibers and endothelial cells, express SPARC. Moreover, SPARC expression levels decline with age in the skeletal muscles of mice. This indicates that although SPARC expression in SMPCs is not altered with age, the amount of SPARC available in the SMPC microenvironment would be decreased. Thus, it is possible that in addition to the decreased responsiveness of SMPC to SPARC, the age-related decline of SPARC expression levels in skeletal muscle accelerates age-related phenotypic changes in SMPC."